Vascular complications constitute the major cause of morbidity and mortality in patients with diabetes mellitus. The mechanisms whereby diabetes results in damage to the large and small blood vessels are largely unknown. In this proposal, we begin to examine the interactions between components of the diabetic process and the endothelial cell, a cell type which forms the inner surface of all blood vessels. We have established primary and passaged cultures of human and bovine endothelium from several different vessels and have demonstrated that the cultured cells retain properties which characterize the endothelial cells in the intact vessel. We have found that all of the cultured endothelial cells possess distinct receptors for insulin and one of the insulin-like growth factors, multiplication stimulating activity (MSA), with the number of specific surface receptors being dependent on the vascular origin of the cultured cell. We will now utilize the endothelial cell cultures to 1) determine the effects of specific components of the diabetic environment on endothelial cell surface receptors and on specific endothelial cell functions 2) assess the effects of insulin and MSA on specialized functions of the endothelial cells and 3) determine the ability of endothelial cells to transport intact insulin and MSA across the endothelium. These studies will require evaluation of hormone-receptor interactions, detailed lipid analysis, extensive use of tissue culture techniques and analysis of proteoglycans. We believe that such studies could demonstrate the multiple areas in which the endothelial cell cultures described in this proposal would then hopefully serve as model systems to furtyer explore the interactions between the endothelium and the diabetic process.